Objective To study the effects of 5-HT1A receptor in hippocampal dentate gyrus on anxiety behavior of adult rats with Parkinson's disease (PD).Methods PD model in rats was constructed by using 6-hydroxydopamine (6-OHDA) to lesion the medial forebrain bundle (MFB).In lesioned rats and sham-operated rats,we examined the changes of the number of TFH-positive neurons in the SNc and VTA.We also examined how 5-HT1A receptor of hippocampal dentate gyrus (DG) modulates the anxiety-related behavior using open field test and elevated plus-maze test,and examined monoamine neurotransmitter changes in the striatum,medial prefrontal cortex (mPFC),amygdale and ventral hippocampus using reverse-phase high performance liquid chromatography with electrochemical detection.Results In 6-OHDA-lesioned rats,the SNc of the injected side showed a total loss of TH-ir neurons compared with the unlesioned side,and the number of TH-ir neurons in the VTA on the lesioned side decreased significantly to (34± 2)％.The locomotor activity in 6-OHDA-lesioned rats decreased compared with that in sham-operated rats.Unilaterally lesioning the MFB decreased the percentage of time spent in the center in the open-field test and percentages of open arm entries and open arm time of elevated plus maze test when compared with sham-operated rats.In the sham-operated rats,intra-DG injection of 8-OH-DPAT did not affect anxiety-like behavior.In 6-OHDA-lesioned rats,intra-DG injection of 8-OH-DPAT significantly increased the percentage of time spent in the center at a dose of 100 ng and 500 ng when compared with saline injection into the DG.Injection of WAY-100635 did not affect rats in the two groups.Unilateral 6-OHDA lesions of the MFB in rats significantly decreased DA levels in the ipsilateral striatum,mPFC,amygdale and ventral hippocampus compared with those in sham-operated rats,but had no effect on 5-HT or NA levels in those structures.Conclusion Unilateral 6-OHDA lesion of the MFB not only totally damaged DA neurons in SNc and partly damaged DA neurons in VTA,but also decreased DA level in the ipsilateral striatum,mPFC,amygdale and ventral hippocampus.Unilateral 6-OHDA lesion of the MFB induces anxiety-related behavior,and activation of 5-HT1A receptor in the hippocampal dentate gyrus has anxiolytic effect in the rat model of Parkinson's disease.%目的 研究背侧海马齿状回5 HT1A受体在制备帕金森病(PD)大鼠焦虑行为中的作用.方法 采用盐酸6-羟基多巴(6-OHDA)单侧内侧前脑束(MFB)完全损毁制备PD模型大鼠.免疫组织化学法观察假手术组和MFB毁损大鼠黑质致密部(SNc)和腹侧被盖区(VTA)酪氨酸羟化酶免疫反应阳性(TH-ir)神经元的数量;采用旷场试验和高架十字迷宫实验观察背侧海马齿状回(DG)局部给予5-HT1A受体激动剂8OH-DPAT或拮抗剂WAY-100635对假手术组和MFB毁损组大鼠焦虑行为的影响;采用高效液相色谱-电化学检测法检测其焦虑相关脑区单胺类神经递质含量的变化.结果 PD组损毁侧SNc中的TH-ir神经元完全缺失,而VTA中TH-ir神经元的数目则显著减少到未损毁侧的(34±2)％;在旷场实验中大鼠的自发运动,包括垂直运动和水平运动能力较假手术组显著降低,并且在旷场实验中央区停留时间和高架十字迷宫实验中的开放臂进入次数百分比和开放臂停留时间百分比均明显缩短,即诱发大鼠的焦虑样行为.背侧海马DG内注射5 HT1A受体激动剂或拮抗剂对大鼠的自发运动均无影响.假手术组大鼠背侧海马DG内微量注射5-HT1A受体激动剂8-OH-DPAT或拮抗剂WAY-100635,均对其焦虑样行为没有影响;而MFB毁损大鼠的背侧海马DG内微量注射8-OH-DPAT,其在旷场试验中央区停留时间显著延长,高架十字迷宫实验开放臂进入次数百分比和开放臂停留时间百分比均显著增加,即改善焦虑样行为;MFB毁损大鼠的背侧海马DG内注射5-HT1A受体拮抗剂WAY-100635,对其焦虑样行为无影响;6-OHDA单侧完全损毁MFB组损伤侧的纹状体、mPFC、杏仁核和腹侧海马内DA神经递质含量明显降低,而5-HT和NA含量没有变化.结论 6-OHDA单侧完全损毁MFB导致SNc的DA能神经元完全损毁,VTA DA能神经元部分损毁;损伤侧的纹状体、mPFC、杏仁核和腹侧海马内DA神经递质含量明显降低,且出现焦虑样行为;背侧海马DG内注射5-HT1A受体激动剂8-OH-DPAT可改善MFB毁损大鼠的焦虑样行为,但对假手术组无影响.
展开▼
